A subpopulation of high IL-21-producing CD4+ T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Jones, Leigh ^a   Ho, Wen Qi ^a   Ying, Sze ^a,b   Ramakrishna, Lakshmi ^a   Srinivasan, Kandhadayar G ^a   Yurieva, Marina ^a   Ng, Wan Pei ^a,c   Subramaniam, Sharrada ^a   Hamadee, Nur H ^a   Joseph, Sabrina ^a   Dolpady, Jayashree ^d   Atarashi, Koji ^e,g   Honda, Kenya ^e,g   Zolezzi, Francesca ^a   Poidinger, Michael ^a   Lafaille, Juan J ^d   Curotto De Lafaille, Maria A ^a,f  

^a AGENCY FOR SCIENCE   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

^d NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e KEIO UNIVERSITY   (Japan)

^f NEW YORK UNIVERSITY   (United States)

^g Institute of Physical and Chemical Research   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 21; INTERLEUKIN DERIVATIVE;

ANIMAL; CD4+ T LYMPHOCYTE; CELL CULTURE; CYTOLOGY; GENETICS; GERMINAL CENTER; IMMUNOLOGY; INTESTINE FLORA; METABOLISM; MICROBIOLOGY; MOUSE; PEYER PATCH; SPLEEN; TRANSGENIC MOUSE;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; GASTROINTESTINAL MICROBIOME; GERMINAL CENTER; INTERLEUKINS; MICE; MICE, TRANSGENIC; PEYER'S PATCHES; SPLEEN;

EID: 84981218340     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep30784     Document Type: Article

References (65)

1. Crotty, S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29, 621-663 (2011).
2. Linterman, M. A., Liston, A., Vinuesa, C. G. T-follicular helper cell differentiation and the co-option of this pathway by non-helper cells. Immunol Rev 247, 143-159 (2012).
3. Breitfeld, D. et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, support immunoglobulin production. J Exp Med 192, 1545-1552 (2000).
4. Schaerli, P. et al. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192, 1553-1562 (2000).
5. Kim, C. H. et al. Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. J Exp Med 193, 1373-1381 (2001).
6. Haynes, N. M. et al. Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J Immunol 179, 5099-5108 (2007).
7. Nurieva, R. I. et al. Bcl6 mediates the development of T follicular helper cells. Science 325, 1001-1005 (2009).
8. Yu, D. et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31, 457-468 (2009).
9. Nurieva, R. I. et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29, 138-149 (2008).
10. Chtanova, T. et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol 173, 68-78 (2004).
11. Ueno, H., Banchereau, J., Vinuesa, C. G. Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol 16, 142-152 (2015).
12. Zotos, D. et al. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med 207, 365-378 (2010).
13. Cao, A. T. et al. Interleukin (IL)-21 promotes intestinal IgA response to microbiota. Mucosal Immunol 8, 1072-1082 (2015).
14. Vogelzang, A. et al. A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 29, 127-137 (2008).
15. Ozaki, K. et al. A critical role for IL-21 in regulating immunoglobulin production. Science 298, 1630-1634 (2002).
16. Seo, G. Y., Youn, J., Kim, P. H. IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer's patches. J Leukoc Biol 85, 744-750 (2009).
17. Kamada, N. et al. Humoral Immunity in the Gut Selectively Targets Phenotypically Virulent Attaching-and-Effacing Bacteria for Intraluminal Elimination. Cell Host Microbe 17, 617-627 (2015).
18. Zeng, M. Y. et al. Gut Microbiota-Induced Immunoglobulin G Controls Systemic Infection by Symbiotic Bacteria and Pathogens. Immunity 44, 647-658 (2016).
19. Brandtzaeg, P., Johansen, F. E. Mucosal B cells: phenotypic characteristics, transcriptional regulation, homing properties. Immunol Rev 206, 32-63 (2005).
20. Fagarasan, S., Kawamoto, S., Kanagawa, O., Suzuki, K. Adaptive immune regulation in the gut: T cell-dependent and T cellindependent IgA synthesis. Annu Rev Immunol 28, 243-273 (2010).
21. Gutzeit, C., Magri, G., Cerutti, A. Intestinal IgA production and its role in host-microbe interaction. Immunol Rev 260, 76-85 (2014).
22. Cebra, J. J., Periwal, S. B., Lee, G., Lee, F., Shroff, K. E. Development and maintenance of the gut-associated lymphoid tissue (GALT): the roles of enteric bacteria and viruses. Developmental immunology 6, 13-18 (1998).
23. Backhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A., Gordon, J. I. Host-bacterial mutualism in the human intestine. Science 307, 1915-1920 (2005).
24. Ott, S. J. et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53, 685-693 (2004).
25. Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202 (2013).
26. Scher, J. U. et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis & rheumatology 67, 128-139 (2015).
27. Kamada, N., Nunez, G. Role of the gut microbiota in the development and function of lymphoid cells. J Immunol 190, 1389-1395 (2013).
28. Kamada, N., Seo, S. U., Chen, G. Y., Nunez, G. Role of the gut microbiota in immunity and inflammatory disease. Nature reviews. Immunology 13, 321-335 (2013).
29. Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337-341 (2011).
30. Ivanov, I. I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337-349 (2008).
31. Luthje, K. et al. The development and fate of follicular helper T cells defined by an IL-21 reporter mouse. Nat Immunol 13, 491-498 (2012).
32. Shulman, Z. et al. Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science 345, 1058-1062 (2014).
33. Harada, Y. et al. The 3? enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral immunity in follicular helper T cells. Immunity 36, 188-200 (2012).
34. Seth, S. et al. Abundance of follicular helper T cells in Peyer's patches is modulated by CD155. Eur J Immunol 39, 3160-3170 (2009).
35. Linterman, M. A. et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med 17, 975-982 (2011).
36. Wang, H. et al. The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells. Nat Immunol 15, 667-675 (2014).
37. Zhou, L. et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8, 967-974 (2007).
38. Nurieva, R. et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448, 480-483 (2007).
39. Mucida, D. et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317, 256-260 (2007).
40. Xiao, S. et al. Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-betadriven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol 181, 2277-2284 (2008).
41. Curotto de Lafaille, M. A. et al. Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes. J Exp Med 194, 1349-1359 (2001).
42. Mucida, D. et al. Oral tolerance in the absence of naturally occurring Tregs. J Clin Invest 115, 1923-1933 (2005).
43. Liu, X., Nurieva, R. I., Dong, C. Transcriptional regulation of follicular T-helper (Tfh) cells. Immunol Rev 252, 139-145 (2013).
44. Linterman, M. A. et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med 207, 353-363 (2010).
45. Ozaki, K. et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol 173, 5361-5371 (2004).
46. Crotty, S. T follicular helper cell differentiation, function, roles in disease. Immunity 41, 529-542 (2014).
47. King, C., Tangye, S. G., Mackay, C. R. T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol 26, 741-766 (2008).
48. Johnston, R. J. et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325, 1006-1010 (2009).
49. Godefroy, E., Zhong, H., Pham, P., Friedman, D., Yazdanbakhsh, K. TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization. Haematologica 100, 1415-1425 (2015).
50. Boles, K. S. et al. A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. Eur J Immunol 39, 695-703 (2009).
51. Tsuji, M. et al. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323, 1488-1492 (2009).
52. Hirota, K. et al. Plasticity of Th17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14, 372-379 (2013).
53. Goenka, R. et al. Cutting edge: dendritic cell-restricted antigen presentation initiates the follicular helper T cell program but cannot complete ultimate effector differentiation. J Immunol 187, 1091-1095 (2011).
54. Deenick, E. K. et al. Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling. Immunity 33, 241-253 (2010).
55. Casola, S. et al. B cell receptor signal strength determines B cell fate. Nat Immunol 5, 317-327 (2004).
56. Lycke, N. Y., Bemark, M. The role of Peyer's patches in synchronizing gut IgA responses. Front Immunol 3, 329 (2012).
57. Suzuki, K. et al. The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut. Immunity 33, 71-83 (2010).
58. Wang, S. et al. MyD88 Adaptor-Dependent Microbial Sensing by Regulatory T Cells Promotes Mucosal Tolerance and Enforces Commensalism. Immunity 43, 289-303 (2015).
59. Bunker, J. J. et al. Innate and Adaptive Humoral Responses Coat Distinct Commensal Bacteria with Immunoglobulin A. Immunity 43, 541-553 (2015).
60. He, B. et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26, 812-826 (2007).
61. Turner, J. R. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9, 799-809 (2009).
62. Bouvet, J. P., Fischetti, V. A. Diversity of antibody-mediated immunity at the mucosal barrier. Infect Immun 67, 2687-2691 (1999).
63. Benckert, J. et al. The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J Clin Invest 121, 1946-1955 (2011).
64. Obata, T. et al. Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis. Proc Natl Acad Sci USA 107, 7419-7424 (2010).
65. Bjerke, K., Brandtzaeg, P. Terminally differentiated human intestinal B cells. J chain expression of IgA and IgG subclass-producing immunocytes in the distal ileum compared with mesenteric and peripheral lymph nodes. Clin Exp Immunol 82, 411-415 (1990).